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Familial Mediterranean fever: Penetrance of the p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=] genotypes
Author(s) -
Eyal Ori,
Shinar Yael,
Pras Mordechai,
Pras Elon
Publication year - 2020
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24090
Subject(s) - penetrance , familial mediterranean fever , genotype , biology , cohort , genetics , population , medicine , disease , gene , phenotype , environmental health
The penetrance of the p.[Met694Val];[Met694Val] genotype of pyrin in adult familial Mediterranean fever (FMF) patients is close to 100%. Disease penetrance of the p.[Met694Val];[Glu148Gln] genotype (M694V/E148Q), and the heterozygous p.[Met694Val];[=] genotype is unknown. A difference in the penetrance of the latter two may indicate functionality for the p.Glu148Gln variant. We performed a penetrance estimation study using controls and patients of North African Jewish (NAJ) decent. FMF in this population is highly prevalent and mutation frequencies are well known. The ratio between the calculated frequencies of the three genotypes obtained from the control cohort and the actual frequency obtained from the patient cohort were used to determine the penetrance of p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=]. We found a penetrance of 0.135 and 0.008 for p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=], respectively. Thus, the penetrance of p.[Met694Val];[Glu148Gln] is more than 17 times higher than p.[Met694Val];[=], indicating an active role for p.Glu148Gln when combined with p.Met694Val.